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Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling

The metazoan Hippo pathway is an essential tumour suppressor signalling cascade that ensures normal tissue growth by co-ordinating cell proliferation, cell death and cell differentiation. Over the past years, various genetic and biochemical studies in Drosophila and mammals have defined a conserved...

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Autor principal: Hergovich, Alexander
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849777/
https://www.ncbi.nlm.nih.gov/pubmed/23985307
http://dx.doi.org/10.1186/2045-3701-3-32
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author Hergovich, Alexander
author_facet Hergovich, Alexander
author_sort Hergovich, Alexander
collection PubMed
description The metazoan Hippo pathway is an essential tumour suppressor signalling cascade that ensures normal tissue growth by co-ordinating cell proliferation, cell death and cell differentiation. Over the past years, various genetic and biochemical studies in Drosophila and mammals have defined a conserved core Hippo signalling module, composed of members of the Ste20-like kinase, the MOB co-activator and the AGC kinase families. In Drosophila, stimulated Hippo kinase phosphorylates and thereby activates the Mats/Warts complex, which consequently phosphorylates and inactivates the transcriptional co-activator Yorkie. In mammals, the counterparts of the Hippo/Mats/Warts/Yorkie cascade, namely MST1/2, MOB1A/B, LATS1/2 and YAP/TAZ, function in a similar fashion. These canonical Hippo pathways are so highly conserved that human MST2, hMOB1A and LATS1 can compensate for the loss of Hippo, Mats and Warts in flies. However, recent reports have shown that Hippo signalling is more diverse and complex, in particular in mammals. In this review, we summarize our current understanding of mammalian LATS1/2 kinases together with their closest relatives, the NDR1/2 kinases. The regulation of the LATS/NDR family of kinases will be discussed, followed by a summary of all currently known LATS/NDR substrates. Last, but not least, the biological roles of LATS/NDR kinases will be reviewed with specific emphasis on recent discoveries of canonical and non-canonical LATS/NDR functions in the extended Hippo pathway.
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spelling pubmed-38497772013-12-05 Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling Hergovich, Alexander Cell Biosci Review The metazoan Hippo pathway is an essential tumour suppressor signalling cascade that ensures normal tissue growth by co-ordinating cell proliferation, cell death and cell differentiation. Over the past years, various genetic and biochemical studies in Drosophila and mammals have defined a conserved core Hippo signalling module, composed of members of the Ste20-like kinase, the MOB co-activator and the AGC kinase families. In Drosophila, stimulated Hippo kinase phosphorylates and thereby activates the Mats/Warts complex, which consequently phosphorylates and inactivates the transcriptional co-activator Yorkie. In mammals, the counterparts of the Hippo/Mats/Warts/Yorkie cascade, namely MST1/2, MOB1A/B, LATS1/2 and YAP/TAZ, function in a similar fashion. These canonical Hippo pathways are so highly conserved that human MST2, hMOB1A and LATS1 can compensate for the loss of Hippo, Mats and Warts in flies. However, recent reports have shown that Hippo signalling is more diverse and complex, in particular in mammals. In this review, we summarize our current understanding of mammalian LATS1/2 kinases together with their closest relatives, the NDR1/2 kinases. The regulation of the LATS/NDR family of kinases will be discussed, followed by a summary of all currently known LATS/NDR substrates. Last, but not least, the biological roles of LATS/NDR kinases will be reviewed with specific emphasis on recent discoveries of canonical and non-canonical LATS/NDR functions in the extended Hippo pathway. BioMed Central 2013-08-28 /pmc/articles/PMC3849777/ /pubmed/23985307 http://dx.doi.org/10.1186/2045-3701-3-32 Text en Copyright © 2013 Hergovich; licensee BioMed Central Ltd. http://creativecommons.org/licenses/by/2.0 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Review
Hergovich, Alexander
Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling
title Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling
title_full Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling
title_fullStr Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling
title_full_unstemmed Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling
title_short Regulation and functions of mammalian LATS/NDR kinases: looking beyond canonical Hippo signalling
title_sort regulation and functions of mammalian lats/ndr kinases: looking beyond canonical hippo signalling
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3849777/
https://www.ncbi.nlm.nih.gov/pubmed/23985307
http://dx.doi.org/10.1186/2045-3701-3-32
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